Inhalation Toxicity of Phosphine for Fischer 344 Rats and B6C3F1 Mice

Abstract

Because of the potential increased use of phosphine (PH₃) as a fumigant and the lack of adequate toxicity data, short-term inhalation studies were conducted to characterize the toxicity of PH₃ for Fischer 344 (F344) rats and B6C3F1 mice. Male rats and mice were exposed to 0, 1, 5, or 10 ppm PH₃ for up to 4 days, and males and females to 0, 1.25, 2.5, or 5 ppm for 2 wk. In the 4-day study, all rats died by the end of the third exposure to 10 ppm, and all mice were euthanized in moribund condition after the fourth exposure to 10 ppm. Clinical pathology data were obtained only for mice, due to early mortality of rats. There were no significant treatment-related effects in hematological indices in mice exposed to 1 or 5 ppm; at 10 ppm there was a moderate anemia, and leukocyte counts were significantly decreased. There were significant biologically relevant increases in serum activity of alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) and in the concentration of urine nitrogen (UN) at 10 ppm. Flectrophoretic evaluation of hemoglobin from mice exposed to 10 ppm did not reveal any differences in banding patterns from controls. Moribund mice euthanized after 4 exposures to 10 ppm had minimal to mild degeneration and necrosis of the renal tubule epithelium, minimal myocardial degeneration, and minimal to mild subcapsular foci of hemorrhage and necrosis in the liver. Bound PH₃ could not be detected in blood, lung, liver, or kidney of mice or lungs of rats exposed to 10 ppm for 3–4 days. There were no treatment-related mortalities in rats or mice exposed for 2 weeks. Lung weights of male rats and mice were significantly decreased and heart weights of female rats and mice were significantly increased after 2 wk of exposure to 5 ppm. Slight but statistically significant increases were observed in serum UN in male mice exposed to 5 ppm. There was no microscopic evidence of treatment-related effects in any of the tissues examined from rats or mice exposed to 5 ppm for 2 wk. Bound PH₃ could not be detected in blood, lung, liver, or kidney of mice or rats exposed to 5 ppm for 2 wk. These studies demonstrated that PH₃ inhalation does not cause a specific target organ toxicity in the B6C3F1 mouse or F344 rat, and that the primary hazard of subchronic inhalation in these species is lethality.